虽然肿瘤生长需要线粒体电子传递链（ETC），但是复合物I（CI）和复合物II（CII）在启动电子流方面的相对贡献尚不清楚。在这项工作中，我们报告说，CII的丧失，而不是CI的丧失，通过增加抗原呈递和T细胞介导的杀伤作用，减少了黑色素瘤的肿瘤生长。这是由丙酸盐介导的转录和表观遗传激活了重要的组织相容性抗原-抗原处理和呈递（MHC-APP）基因，与干扰素信号独立。此外，甲基化控制的J蛋白（MCJ）的敲除，优先通过CI促进电子进入，提供了ETC重构实现抗肿瘤应答的概念验证，而不会出现与非癌细胞线粒体呼吸总体减少相关的副作用。我们的结果可能对于具有MHC-APP表达降低的肿瘤有治疗潜力，而这是癌症免疫逃逸的一种常见机制。

Although tumor growth requires the mitochondrial electron transport chain (ETC), the relative contribution of complex I (CI) and complex II (CII), the gatekeepers for initiating electron flow, remains unclear. In this work, we report that the loss of CII, but not that of CI, reduces melanoma tumor growth by increasing antigen presentation and T cell-mediated killing. This is driven by succinate-mediated transcriptional and epigenetic activation of major histocompatibility complex-antigen processing and presentation (MHC-APP) genes independent of interferon signaling. Furthermore, knockout of methylation-controlled J protein (MCJ), to promote electron entry preferentially through CI, provides proof of concept of ETC rewiring to achieve antitumor responses without side effects associated with an overall reduction in mitochondrial respiration in noncancer cells. Our results may hold therapeutic potential for tumors that have reduced MHC-APP expression, a common mechanism of cancer immunoevasion.